Experimental and Clinical Neurotoxicology

by Spencer, Peter S.; Schaumburg, Herbert H.; Ludolph, Albert C.

• ISBN13: 9780195084771
• ISBN10: 0195084772
• Edition: 2nd
• Format: Hardcover
• Copyright: 2000-03-09
• Publisher: Oxford University Press

Summary

Two decades have passed since publication of the first edition of Experimental and Clinical Neurotoxicology pioneered the development of this discipline. Since then no other book has approached the breadth, scholarship, and balance of that landmark volume. For this long-awaited second edition,the original editors have been joined by Albert Ludolf, who brings expertise in biological neurotoxicology, and together with their distinguished contributors they have completely rewritten and reorganized the text. The scientific and clinical foundation is laid in three comprehensive introductory chapters. An overview of the biological basis of neurotoxicity provides the goundwork for discussing the scope of human and veterinary neurotoxic disease.The bulk of the text is devoted to an alphabeticaltreatment of chemicals with neurotoxic potential. This consists of tightly written overviews of the properties, actions, and mechanisms of all manner of substances, whether natural or synthetic. The neurotoxic side effects of experimental agents and of therapeutic as well as abused drugs arecovered extensively. Environmental pollutants, workplace contaminants, personal-use products, food additives, and agents harbored by plants, animals, and humans for use against their respective enemies are discussed. Each substance is rated on a three-point scale for the weight of evidenceindicating a specific neurotoxic effect in humans, animals, or laboratory models. These effects are summarized and cross-referenced in a series of appendices and an extensive index. In summary, the second edition establishes neurotoxicology as a scientific discipline that melds neurobiology, toxicology, and neurology. From this unique vantage point, the book examines in encyclopedic manner several hundred chemicals with the capacity to induce neurological illness in humansand animals. Indispensable for the experimental neuroscientist and toxicologist, as well as for practitioners of human and animal medicine, the book also provides an authoritative, critical, and pithy reference work for specialists in public health and the legal profession.

Table of Contents

PART ONE FUNDAMENTALS OF EXPERIMENTAL AND CLINICAL NEUROTOXICOLOGY
Biological Principles of Chemical Neurotoxicity	3	(52)
Peter S. Spencer
Vulnerability of The Nervous System	3	(10)
Extraneural Factors	4	(1)
Exposure, Dose and Response	4	(2)
Biotransformation	6	(1)
Species, Genotype, Gender, Nutrition, Age	6	(1)
Factors Associated with the Nervous System	7	(1)
Neural Microenvironment	7	(3)
Architectural and Functional Specialization	10	(2)
Nature and Progress of the Neurotoxic Response	12	(1)
Vulnerability of Neurons and Their Processes	13	(27)
Somal DNA	13	(1)
Protein Synthesis and Enzyme Inhibition	13	(1)
Mitochondria and Energy State	14	(1)
Vitamin Function	15	(2)
Physiological lons	17	(1)
G Proteins	17	(1)
Excitable Membrane	18	(1)
Sodium lon (Na+) Channels	18	(2)
Potassium lon (K+) Channels	20	(1)
Chloride lon (Cl-) Channels	21	(1)
Calcium lon (Ca2+) Channels	22	(1)
lonophores	23	(1)
Neurotransmitter Systems	23	(1)
Exocytosis	23	(1)
Acetylcholine	24	(3)
Glutamate/Aspartate	27	(4)
GABA	31	(1)
Glycine	32	(1)
Catecholamines	32	(2)
Serotonin	34	(1)
Neuropeptides	35	(2)
Cannabinoid Receptors	37	(1)
Purinoceptors and Adenosine Receptors	37	(1)
Axonal Transport	37	(2)
Vesicles	39	(1)
Cytoskeletal Proteins	39	(1)
Vulnerability of Neuroglia and Myelin	40	(1)
Astrocytes and Ependymal Cells	40	(1)
Oligodendrocytes and Schwann Cells	40	(1)
System Vulnerability to Chemicals	41	(9)
Special Senses	41	(1)
Olfaction	42	(1)
Gustation	43	(1)
Vision	43	(1)
Balance and Audition	43	(1)
Sensorimotor Function	44	(1)
Principal Sensory Pathway	45	(1)
Pain Pathways	45	(1)
Principal (Voluntary) Motor Pathway	46	(1)
Cerebellum	46	(1)
Basal Ganglia	47	(1)
Autonomic (Involuntary) Motor System	48	(1)
Hypothalamus, Hippocampus and Limbic System	49	(1)
Developmental Neurotoxicity	50	(3)
Sensitive Periods of Neural Development	50	(1)
Fetal and Newborn Toxic Syndromes	51	(2)
CNS and PNS Chemical Oncogenesis	53	(1)
Selected Bibliography	54	(1)
Human Neurotoxic Disease	55	(28)
Herbert H. Schaumburg
Causation Criteria for Identification of Neurotoxicity	55	(1)
Cardinal Tenets of Neurotoxic Disease	56	(1)
Strong Dose-response Relationship	56	(1)
Proximity to Exposure	56	(1)
Improvement Usually Follows Cessation of Exposure	56	(1)
Multiple Clinical Syndromes May Result from Different Exposures to a Single Toxin	56	(1)
Asymptomatic Disease	56	(1)
Modulation by Bystander Chemicals	57	(1)
Chemical Formula May Not Predict Toxicity	57	(1)
Age, Pre-existing Conditions or Genetic Variation in Metabolism Occasionally Modulate the Effects of a Neurotoxin	57	(1)
The Nature of Neurotoxic Disease	57	(16)
Neurotoxic Clinical Syndromes (corresponds generally to Clinical Neurotoxicity Rating Scale for substances in A--Z catalogue section)	57	(1)
Pseudo Neurotoxic Syndromes	57	(1)
Physical Dependence/Addiction/Abuse	58	(1)
Psychobiological Reactions	59	(1)
Acute Encephalopathy Syndromes (Cortical-Subcortical Neuronal Encephalopathy/Leukoencephalopathy)	59	(2)
Neuroleptic Malignant Syndrome	61	(1)
Malignant Hyperthermia Syndrome	61	(1)
Chronic Encephalopathy Syndromes	61	(1)
Dementia	62	(1)
Seizure Disorders	62	(1)
Headache Syndromes	63	(1)
Pyramidal Syndrome	63	(1)
Extrapyramidal Syndromes	64	(1)
Cerebellar Syndromes	65	(1)
Hydrocephalus	65	(1)
Benign Intracranial Hypertension (Pseudotumor Cerebri)	65	(1)
Aseptic Meningitis	65	(1)
Encephalomalacia (stroke)	65	(1)
Tremor	65	(1)
Neural Visual System	66	(1)
Neural Auditory and Vestibular Systems (Ototoxicity)	66	(1)
Olfaction and Taste	67	(1)
Myelopathy (Spinal Cord)	68	(1)
Peripheral Neuropathy	68	(1)
Sensory Neuronopathy Syndrome	69	(1)
Cranial Neuropathy	70	(1)
lon Channel Syndromes	70	(1)
Neuromuscular Transmission Syndromes	71	(1)
Myopathy	71	(1)
Specific Syndromes and Scenarios Strongly Associated with Neurotoxins	72	(1)
Assessment of Neurotoxic Disease in Individuals	73	(5)
Methods and Procedures	73	(1)
History	74	(1)
Physical Examination	74	(1)
Neuropsychological Tests	74	(1)
Specialized Laboratory Tests	75	(1)
Illustrative Clinical Vignettes	76	(1)
Pseudo Neurotoxic Syndromes	76	(1)
Neurotoxic PNS Syndromes	77	(1)
Neurotoxic CNS Syndromes	77	(1)
Assessment of Neurotoxic Disease in Large Populations	78	(5)
Study Design	78	(1)
Methods and Procedures	79	(1)
Questionnaire	79	(1)
Quantitative Sensory Testing	79	(1)
Tremor Analysis	79	(1)
Computer-administered Neurobehavioral Testing	79	(1)
Biological Markers	79	(1)
Data Analysis	80	(1)
Large-population Screening Scenarios	81	(2)
Aspects of Veterinary Neurotoxicology	83	(26)
Anthony A. Frank
Linda L. Blythe
Peter S. Spencer
Host Factors	83	(1)
Nonbiological Neurotoxic Factors	84	(5)
Feed, Chemicals, and Water	84	(1)
Metals, Metalloids and Other Elements	85	(1)
Arsenic	85	(1)
Boron	85	(1)
Lead	85	(1)
Mercurials	85	(1)
Molybdenum intoxication/copper deficiency	86	(1)
Selenium	86	(1)
Sulfide/Sulfate-induced Polioencephalomalacia	86	(1)
Fungicides, Pesticides, Herbicides, Baits, and Repellants	87	(1)
4-Aminopyridine	87	(1)
Bromethalin	87	(1)
α-Chloralose	88	(1)
N, N-Diethyl-m-toluamide-fenvalerate	88	(1)
Fluoroacetate	88	(1)
d-Limonene	88	(1)
Metaldehyde	88	(1)
Strychnine	88	(1)
Biological Neurotoxic Factors	89	(20)
Bacteria	89	(1)
Clostridium perfringens Type D	89	(1)
Corynebacterium rathayi	89	(1)
Blue-green Algae	89	(1)
Fungal Neurotoxins	90	(1)
Tremorgens	90	(1)
Other Myconeurotoxins	91	(1)
Neurotoxic Plants	92	(1)
Neurodegenerative Disorders	93	(1)
Optic Nerve Damage	93	(1)
Extrapyramidal and Movement Disorders	93	(1)
Motoneuron and Locomotor Disorders	94	(1)
Neuronal Storage Disorders	95	(1)
Strychnine-like and Other Convulsant Effects	96	(1)
Effects on Cholinergic Neurotransmission: Anticholinesterase Effects	97	(1)
Nicotinic Receptor Blockade	97	(1)
Nicotine-like Toxins	97	(1)
Disorders of Striated Muscle	97	(2)
Disorders of Cardiac Muscle	99	(10)
PART TWO SUBSTANCES WITH NEUROTOXIC POTENTIAL
Neurotoxic Substances
Criteria for Neurotoxicity	109	(1)
Absinthe (Wormwood)	109	(1)
Albert C. Ludolph
Herbert H. Schaumburg
Acacia berlandieri Benth.	110	(1)
Albert C. Ludolph
Acetone	111	(1)
Herbert H. Schaumburg
Acetyl Ethyl Tetramethyl Tetralin	112	(4)
Peter S. Spencer
3-Acetylpyridine	116	(2)
Hans Kolbe
Acetylsalicylic Acid	118	(3)
Peter C. Mabie
Acivicin	121	(1)
Herbert H. Schaumburg
Aconitine	122	(1)
Peter S. Spencer
Acromelic Acid	123	(1)
Albert C. Ludolph
Acrylamide	124	(9)
Bruce G. Gold
Herbert H. Schaumburg
Acrylonitrile	133	(2)
Kevin M. Crofton
Mary Beth Genter
Acyclovir	135	(1)
Herbert H. Schaumburg
Agaritine	136	(1)
Peter S. Spencer
Agatoxins	137	(1)
Albert C. Ludolph
L-Alanosine A	138	(1)
Albert C. Ludolph
Allyl Chloride	139	(1)
Fengsheng He
Allylglycine	140	(1)
Albert C. Ludolph
Almitrine Bimesilate	141	(1)
Herbert H. Schaumburg
Aluminum and Its Compounds	142	(9)
Peter S. Spencer
Amanita Toxins	151	(2)
Albert C. Ludolph
Amantadine	153	(1)
John D. Rogers
α-Aminoadipic Acid	153	(1)
Albert C. Ludolph
&epsis;-Aminocaproic Acid	154	(2)
Daniel M. Rosenbaum
1-Amino-3-Chloro-2-Propanol	156	(1)
Peter S. Spencer
Aminoglycoside Antibiotics (Streptomycin)	156	(5)
Herbert H. Schaumburg
6-Aminonicotinamide	161	(4)
Hans Kolbe
α-Aminopyridine	165	(1)
Albert C. Ludolph
Amiodarone	166	(3)
Steven Herskovitz
Amoscanate	169	(1)
Georg J. Krinke
Amphetamines and Related Compounds	170	(22)
Alfred Heller
Lisa Won
Philip C. Hoffmann
Amphotericin B	192	(1)
Herbert H. Schaumburg
Amsacrine	193	(1)
Albert C. Ludolph
A-MTX	194	(1)
Albert C. Ludolph
Amyl Alcohols	194	(1)
Herbert H. Schaumburg
Anabasine	195	(1)
Albert C. Ludolph
Anatoxins	196	(3)
Wayne W. Carmichael
Edward G. Hyde
Anisatin	199	(1)
Peter S. Spencer
Anthranilic Acid and Derivatives	199	(1)
Albert C. Ludolph
Antillatoxin	199	(1)
William H. Gerwick
Thomas F. Murray
Apamin and Hymenoptera Venoms	200	(3)
Zarife Sahenk
Jerry R. Mendell
Arsenic	203	(4)
Anthony J. Windebank
1-Aryl-3,3-Dialkyltriazenes	207	(1)
Peter S. Spencer
L-Asparaginase	208	(1)
Herbert H. Schaumburg
Aspartame	209	(3)
Bennett A. Shaywitz
Atropine	212	(2)
Brent T. Burton
Avermectins	214	(2)
Albert C. Ludolph
Azacitidine	216	(1)
Herbert H. Schaumburg
Azoles	217	(2)
Herbert H. Schaumburg
Baclofen	219	(1)
Herbert H. Schaumburg
Barbiturates	219	(6)
Joseph Maytal
Shlomo Shinnar
Barium	225	(2)
Steven Herskovitz
Batrachotoxin and Related Compounds	227	(1)
Peter S. Spencer
Benzalkonium Chloride	228	(1)
Peter S. Spencer
Benzene	228	(1)
Herbert H. Schaumburg
Benzene Hexachloride	229	(1)
Herbert H. Schaumburg
Benzimidazole	230	(1)
Herbert H. Schaumburg
Benzodiazepines	231	(4)
Howard A. Crystal
Herbert H. Schaumburg
Bicuculline	235	(1)
Albert C. Ludolph
Bismuth	236	(3)
Mark Forest Gordon
Black Widow Spider Venom	239	(4)
Alfredo Gorio
Anna Maria Di Giulio
Botulinum Neurotoxin	243	(9)
Phyllis L. Bieri
Bradykinin Analogs	252	(2)
Tom Piek
Brevetoxins	254	(1)
Albert C. Ludolph
Bromide	255	(2)
Peter C. Mabie
Bromocriptine	257	(1)
John D. Rogers
p-Bromophenylacetylurea	258	(2)
Richard M. LoPachin
Ellen J. Lehning
p-Bromophenylisothiocyanate	260	(1)
John L. O'Donoghue
Buspirone	260	(1)
Herbert H. Schaumburg
2-Butenenitrile	261	(2)
Kevin M. Crofton
Mary Beth Genter
3-Butenenitrile	263	(2)
Kevin M. Crofton
Mary Beth Genter
Buthotus hottentota	265	(1)
Albert C. Ludolph
2-t-Butylazo-2-hydroxy-5-methylhexane	265	(3)
Thomas L. Kurt
N-Butylbenzenesulfonamide	268	(1)
Albert C. Ludolph
6-tert-Butyl-3-methyl-2,4-dinitroanisole	269	(2)
Peter S. Spencer
γ-Butyrolactone	271	(1)
Peter S. Spencer
Butyrophenones	272	(4)
Matthias Riepe
Cadmium	276	(4)
J. Michael Schroder
Calycanthine	280	(1)
Albert C. Ludolph
Canatoxin	280	(1)
Albert C. Ludolph
Cannabis	281	(3)
John C. M. Brust
Cantharidin	284	(1)
Herbert H. Schaumburg
Capsaicin and Analogs	284	(4)
Rainer Amann
Peter Holzer
Captopril	288	(1)
Herbert H. Schaumburg
Carbamates	289	(9)
Donald J. Ecobichon
Carbamazepine	298	(6)
Carol Eisenberg
Mark J. Sinnett
Shlomo Shinnar
Carbolines/Isoquinolines	304	(11)
Michael A. Collins
Edward J. Neafsey
Carbon Disulfide	315	(3)
Doyle G. Graham
William M. Valentine
Carbon Monoxide	318	(12)
Howard A. Crystal
Myron D. Ginsberg
Carbon Tetrachloride	330	(3)
John L. O'Donoghue
Carboxyatractyloside	333	(1)
Albert C. Ludolph
Carmustine	334	(4)
William C. Welch
Paul L. Kornblith
Cassava	338	(6)
Hans Rosling
Thorkild Tylleskar
Catha edulis	344	(1)
Matthias Riepe
Cephalosporins	345	(3)
Libor Velisek
Solomon L. Moshe
Ceruleotoxin	348	(1)
Albert C. Ludolph
CGS 21595	349	(1)
Georg J. Krinke
Charatoxin	350	(1)
Albert C. Ludolph
Charybdotoxin	351	(1)
Albert C. Ludolph
Cheilanthes sieberi	352	(1)
Albert C. Ludolph
Chelidonium majus	353	(1)
Albert C. Ludolph
Chloral Hydrate	353	(1)
Herbert H. Schaumburg
Chloramphenicol	354	(1)
Herbert H. Schaumburg
Chlordecone	355	(8)
John R. Taylor
John B. Selhorst
Vincent P. Calabrese
Martha Neff-Smith
Chlorhexidine Gluconate	363	(1)
Herbert H. Schaumburg
Chlorinated Cyclodienes	364	(7)
Peter S. Spencer
Herbert H. Schaumburg
6-Chloro-6-Deoxyglucose	371	(1)
Peter S. Spencer
(2-Chloroethyl)-N-ethyl-2-bromobenzylamine	372	(1)
Albert C. Ludolph
2-Chloropropionic Acid	373	(2)
John L. O'Donoghue
Chloroquine	375	(4)
William A. Meier-Ruge
Herbert H. Schaumburg
Chlorpromazine and Other Neuroleptics	379	(6)
Arnold E. Merriam
Cicutoxin	385	(1)
Albert C. Ludolph
Ciguatoxin	386	(5)
Jerry G. Kaplan
Cimetidine	391	(1)
Herbert H. Schaumburg
Cinnarizine	391	(1)
John D. Rogers
Cisplatin	392	(4)
Anthony J. Windebank
Clioquinol	396	(5)
Herbert H. Schaumburg
Clioxanide	401	(1)
Albert C. Ludolph
Clofibrate	401	(2)
Bryon A. Kakulas
Clonidine	403	(1)
Herbert H. Schaumburg
Clozapine	404	(2)
Albert C. Ludolph
Clupeotoxin	406	(1)
Albert C. Ludolph
Peter S. Spencer
Cobra Venom	407	(1)
Albert C. Ludolph
Cocaine	408	(5)
Randall Berliner
Colchicine	413	(2)
Herbert H. Schaumburg
Conium maculatum	415	(2)
Albert C. Ludolph
Peter S. Spencer
Conotoxins	417	(3)
Lourdes J. Cruz
Baldomero M. Olivera
Corticosteroids	420	(3)
Byron A. Kakulas
Cotyledon Spp.	423	(1)
Albert C. Ludolph
Crotalaria Spp.	423	(1)
Albert C. Ludolph
Crotamine	424	(1)
Albert C. Ludolph
Crotoxin	425	(1)
Albert C. Ludolph
Cuprizone	426	(2)
Thomas W. Bouldin
Cyanides and Related Compounds	428	(8)
John Tor-Agbidye
Peter S. Spencer
Cycasin, Methylazoxymethanol and Related Compounds	436	(11)
Peter S. Spencer
Glen Kisby
Valerie S. Plamer
Peter Obendorf
Cyclobenzaprine	447	(1)
Herbert H. Schaumburg
Cycloleucine	448	(3)
Henry C. Powell
Cyclopentolate	451	(1)
Herbert H. Schaumburg
Cycloserine	452	(1)
Herbert H. Schaumburg
Peter S. Spencer
Cyclosporine	453	(2)
Matthias Riepe
Herbert H. Schaumburg
Cyclotrimethylenetrinitramine	455	(2)
Steven A. Sparr
L-Cysteine	457	(1)
John W. Olney
Cytarabine	458	(5)
Mark F. Mehler
Dactinomycin (Actinomycin D)	463	(1)
Herbert H. Schaumburg
Dapsone	464	(2)
Ludwig Guttmann
Datura Stramonium	466	(1)
Albert C. Ludolph
Delphinium Spp.	467	(2)
Albert C. Ludolph
Dendroaspis angusticeps Toxins	469	(3)
Frank Bretschneider
Albert C. Ludolph
20,25-Diazacholesterol	472	(2)
Jorge N. Larocca
Dichloroacetic Acid	474	(2)
Peter S. Spencer
Dichloroacetylene	476	(2)
Herbert H. Schaumburg
Dichlorodiphenyltrichloroethane and Derivatives	478	(5)
Peter S. Spencer
Herbert H. Schaumburg
2,4-Dichlorophenoxyacetic Acid	483	(3)
Herbert H. Schaumburg
Dideoxycytidine and Other Nucleoside Analogs	486	(4)
Joseph C. Arezzo
Diethylbenzene	490	(2)
Peter S. Spencer
N,N-Diethyl-m-toluamide and Other Dialkylamides	492	(5)
Peter S. Spencer
Digitalis and Other Cardiac Glycosides	497	(2)
Daniel M. Rosenbaum
Dihydro-β-erythroidine	499	(1)
Albert C. Ludolph
N,N'-Dimethylaminopropionitrile	499	(3)
Alan Pestronk
Dimethyl Sulfate	502	(1)
Peter S. Spencer
Diphenyl	503	(2)
Peter S. Spencer
Diphtheria Toxin	505	(6)
Herbert H. Schaumburg
Dennis A. Aquino
Kenneth R. Einberg
Dipiperidinoethane	511	(1)
Albert C. Ludolph
Disulfiram	512	(2)
John C. M. Brust
2,4-Dithiobiuret	514	(3)
John L. O'Donoghue
Dizocilpine	517	(1)
Albert C. Ludolph
Domoic Acid	518	(11)
Neil R. Cashman
F. Cendes
Doxorubicin and Related Anthracyclines	529	(5)
Peter S. Spencer
Enflurane	534	(1)
Herbert H. Schaumburg
Erabutoxins	534	(1)
Albert C. Ludolph
Ergot Alkaloids	535	(2)
Lawrence C. Newman
Richard B. Lipton
Erythromycin	537	(1)
Herbert H. Schaumburg
Ethacrynic Acid	538	(1)
Herbert H. Schaumburg
Ethambutol	539	(2)
Peter S. Spencer
Ethanol	541	(17)
John C. M. Brust
Ethchlorvynol	558	(1)
Herbert H. Schaumburg
Ethidium Bromide	558	(2)
Peter S. Spencer
Ethionamide	560	(1)
Herbert H. Schaumburg
Ethylcholine Aziridinium	561	(1)
Peter S. Spencer
Ethylene Glycol	562	(1)
Herbert H. Schaumburg
Ethylene Oxide	563	(3)
Akio Ohnishi
Euphorbia Spp.	566	(1)
Thomas Meyer
Albert C. Ludolph
Fasciculins	567	(1)
Albert C. Ludolph
Fentanyl	568	(1)
John C. M. Brust
Flecanide and Other Class 1c Antiarrhythmic Agents	569	(2)
Steven A. Sparr
Fludarabine	571	(3)
Mark F. Mehler
Flumazenil	574	(1)
Herbert H. Schaumburg
Flunarazine	574	(1)
John D. Rogers
Fluoroacetic Acid	575	(3)
Hans Kolbe
Fluoroquinolones	578	(1)
Herbert H. Schaumburg
5-Fluorouracil	579	(3)
Mark F. Mehler
Fluoxetine and Other Serotonin-Reuptake Blockers	582	(2)
Arnold E. Merriam
Fumitremorgen	584	(2)
Albert C. Ludolph
Fumonisin	586	(1)
Albert C. Ludolph
Funnel-Web Spider Toxins	587	(1)
Albert C. Ludolph
Peter S. Spencer
Furaltadone	588	(1)
Herbert H. Schaumburg
Furosemide	589	(1)
Herbert H. Schaumburg
Galactose	590	(5)
Andrew P. Mizisin
Henry C. Powell
Ganciclovir	595	(3)
Steven A. Sparr
Gangliosides	598	(2)
Horst Wietholter
Gasoline	600	(1)
Herbert H. Schaumburg
Germanium Dioxide	600	(2)
Herbert H. Schaumburg
Germine	602	(1)
Albert C. Ludolph
Gila Monster Venom	603	(1)
Albert C. Ludolph
Ginseng	603	(1)
Herbert H. Schaumburg
Glutamic Acid	604	(6)
John W. Olney
Albert C. Ludolph
Glutethimide	610	(1)
Albert C. Ludolph
α-Glycerotoxins	611	(1)
Albert C. Ludolph
Frank Bretschneider
Glycine	612	(2)
Thomas L. Slamovits
Gold Salts	614	(1)
Steven Herskovitz
Gossypol	615	(2)
Fengsheng He
Grammostola spatulata	617	(1)
Albert C. Ludolph
Grayanotoxins	617	(1)
Albert C. Ludolph
Griseofulvin	618	(1)
Herbert H. Schaumburg
Gyromitrin	619	(2)
Albert C. Ludolph
Halothane	621	(1)
Herbert H. Schaumburg
Helichrysum Spp.	621	(1)
Helge Volkel
Albert C. Ludolph
n-Heptane	622	(1)
Herbert H. Schaumburg
Heroin	623	(3)
John C. M. Brust
Hexachlorobenzene	626	(4)
Henry A. Peters
Derek J. Cripps
Ayhan Gocmen
George T. Bryan
Hexachlorophene	630	(2)
Mitchell Steinschneider
2,4-Hexadiene-1-nitrile	632	(1)
John L. O'Donoghue
Hexamethylmelamine	632	(1)
Herbert H. Schaumburg
n-Hexane, Metabolites, and Derivatives	633	(15)
Anthony P. DeCaprio
Histrionicotoxins	648	(1)
Alexander Storch
Albert C. Ludolph
Holothurins and Holotoxins	649	(1)
Peter S. Spencer
Hydralazine	650	(2)
Glen Kisby
Hydrazine	652	(3)
Glen Kisby
Hydrogen Sulfide	655	(3)
D. Gary Rischitelli
Herbert H. Schaumburg
Hydrophiidae Toxins	658	(1)
Albert C. Ludolph
6-Hydroxydopamine	659	(8)
Hans Georg Baumgarten
Zarko Grozdanovic
α-Hydroxytoluene	667	(2)
Peter S. Spencer
Hymenoxys richardsonii	669	(1)
Helge Volkel
Albert C. Ludolph
Hypoglycine	669	(4)
Peter S. Spencer
Iberiotoxin	673	(1)
Albert C. Ludolph
Ibotenic Acid	673	(1)
Albert C. Ludolph
Ibuprofen	674	(1)
Herbert H. Schaumburg
Ifosfamide	675	(3)
Steven A. Sparr
β,β′-Iminodipropionitrile	678	(2)
Bruce G. Gold
Indolealkylamines	680	(1)
Albert C. Ludolph
Indomethacin	681	(2)
Steven A. Sparr
Interferon-α	683	(1)
Herbert H. Schaumburg
Iodoacetate	684	(1)
Albert C. Ludolph
Peter S. Spencer
Iohexol and Other Radiographic Contrast Agents	685	(4)
George Lantos
Ipomoea Spp.	689	(1)
Matthias W. Riepe
Isoflurane	690	(1)
Herbert H. Schaumburg
Isoniazid	690	(7)
J. Michael Schroder
Isopropanol	697	(1)
Herbert H. Schaumburg
Isoxazololes	698	(2)
Matthias W. Riepe
Janthitrems	700	(1)
Albert C. Ludolph
JSTX-3	701	(2)
Nobufumi Kawai
Kaliotoxin	703	(1)
Albert C. Ludolph
Kallstroemia hirsutissima	703	(1)
Alexander Storch
Albert C. Ludolph
Kalmia latifolia	704	(1)
Albert C. Ludolph
Karwinskia humboldtiana	705	(3)
Roy O. Weller
Lead, Inorganic	708	(12)
Deborah A. Cory-Schlecta
Herbert H. Schaumburg
Lead, Organic	720	(1)
Herbert H. Schaumburg
Leiurotoxin	721	(1)
Albert C. Ludolph
Leptinotoxin H	722	(1)
Albert C. Ludolph
Levamisole	722	(1)
Herbert H. Schaumburg
Levodopa	723	(3)
John D. Rogers
Lidocaine and Related Local Anesthetics	726	(10)
Michael W. Kalichman
Henry C. Powell
Lincomycin	736	(1)
Steven Herskovitz
Lithium	737	(4)
Klaus Windgassen
Lobeline	741	(1)
John C. M. Brust
Lophotoxin and Other Gorgonian Toxins	742	(1)
Albert C. Ludolph
Lovastatin	743	(1)
Herbert H. Schaumburg
Lupinus Spp.	744	(1)
Thomas Meyer
Albert C. Ludolph
Lysergide	745	(2)
Arnold E. Merriam
Lysolecithin	747	(3)
Thomas W. Bouldin
Maitotoxin	750	(1)
Albert C. Ludolph
Mamba Snake Venom	751	(1)
Albert C. Ludolph
Mandaratoxin	752	(1)
Albert C. Ludolph
Manganese	752	(4)
Nai-Shin Chu
Chin-Chang Huang
Donald B. Calne
Margatoxin	756	(1)
Albert C. Ludolph
Measles Vaccine	756	(1)
Neil L. Rosenberg
Mechlorethamine	757	(2)
Herbert H. Schaumburg
Mefloquine	759	(2)
Steven A. Sparr
Meperidine	761	(1)
John C. M. Brust
3-Mercaptopropionic Acid	762	(1)
Peter S. Spencer
Mercury and Mercury Compounds	763	(7)
M. Anthony Verity
Ted A. Sarafian
Mescaline	770	(2)
John C. M. Brust
Methadone	772	(1)
John C. M. Brust
Methanol	773	(7)
Albert C. Ludolph
Methaqualone	780	(1)
John C. M. Brust
Methionine Sulfoximine	781	(3)
Mohammad I. Sabri
Methohexital Sodium	784	(1)
Albert C. Ludolph
Methotrexate	785	(4)
Raul Francisco Valenzuela
Fred H. Hochberg
Methoxyflurane	789	(1)
Herbert H. Schaumburg
β-N-Methylamino-L-Alanine	789	(5)
Glen Kisby
Methyl Bromide	794	(2)
Steven Herskovitz
Methyl Chloride	796	(2)
Peter S. Spencer
Methylene Chloride	798	(4)
Richard D. Stewart
Herbert H. Schaumburg
3,4-Methylenedioxymethamphetamine	802	(5)
William Slikker Jr.
Herbert H. Schaumburg
Methyl Ethyl Ketone	807	(1)
Herbert H. Schaumburg
3,3'-Methyliminobis(N-Methylpropylamine)	807	(1)
Peter S. Spencer
Methyl lodide	807	(2)
Peter S. Spencer
Methyllycaconitine	809	(1)
Albert C. Ludolph
Methyl Methacrylate	810	(2)
Steven Herskovitz
MPTP and Analogs	812	(7)
Donato A. Di Monte
J. William Langston
Methylxanthines	819	(2)
Albert C. Ludolph
Methysergide	821	(1)
Herbert H. Schaumburg
Metoclopramide	822	(3)
Steven A. Sparr
Metrizamide	825	(2)
Steven Herskovitz
Metronidazole	827	(1)
Steven Herskovitz
Misonidazole	828	(2)
Steven Herskovitz
Mitotane	830	(1)
Herbert H. Schaumburg
MMR Vaccine	830	(2)
Neil L. Rosenberg
Mojave Toxin	832	(1)
Albert C. Ludolph
Morphine and Related Opiates	833	(3)
John C. M. Brust
Mumps Vaccine	836	(1)
Neil L. Rosenberg
Mustard Warfare Agents and Related Substances	837	(11)
Peter S. Spencer
Jeffrey L. Daniels
Glen Kisby
Muzolimine	848	(1)
Herbert H. Schaumburg
Myristica fragrans	849	(3)
Frank Bretschneider
Albert C. Ludolph
Nalidixic Acid	852	(2)
Steven A. Sparr
Naphthalene	854	(1)
John D. Rogers
1-Naphthylacetyl Spermine	854	(1)
Nobufumi Kawai
Naproxen	855	(2)
Herbert H. Schaumburg
Neosurugatoxin	857	(1)
Albert C. Ludolph
Nereistoxin and Related Compounds	858	(2)
William R. Kem
Nicotine	860	(2)
John C. M. Brust
Nifedipine	862	(2)
Steven A. Sparr
Nitrobenzene	864	(2)
John L. O'Donoghue
Nitrofurantoin	866	(3)
Herbert H. Schaumburg
Nitrogen Trichloride	869	(1)
John L. O'Donoghue
3-Nitropropionic Acid and Related Compounds	870	(5)
Fengsheng He
Albert C. Ludolph
Nitroprusside	875	(1)
Herbert H. Schaumburg
Nitrosoureas	876	(6)
Glen Kisby
Nitrous Oxide	882	(7)
Stephen N. Scelsa
Noxiustoxin	889	(2)
Albert C. Ludolph
Peter S. Spencer
Ochratoxins	891	(1)
Albert C. Ludolph
Peter S. Spencer
Okadaic Acid	892	(2)
Peter S. Spencer
Organic Solvent Mixtures	894	(4)
Herbert H. Schaumburg
Peter S. Spencer
Organophosphorus Compounds	898	(28)
Marcello Lotti
β-N-Oxalylamino-L-Alanine	926	(13)
Jacques Hugon
Albert C. Ludolph
Peter S. Spencer
Oxotremorine	939	(1)
Albert C. Ludolph
Peter S. Spencer
Oxybate	939	(1)
Peter S. Spencer
Palytoxin	940	(2)
Alexander Storch
Albert C. Ludolph
Pandinus imperator Toxin	942	(1)
Albert C. Ludolph
Peter S. Spencer
Paraquat	943	(1)
Herbert H. Schaumburg
Parmelia molliuscula	944	(1)
Albert C. Ludolph
Pelamitoxin	944	(1)
Albert C. Ludolph
Pemoline	944	(2)
Herbert H. Schaumburg
Penicillamine	946	(2)
Steven Herskovitz
Penicillins	948	(3)
Libor Velisek
Solomon L. Moshe
Penitrems and Other Tremorgens	951	(12)
Albert C. Ludolph
Peter S. Spencer
Pennyroyal Oil	963	(1)
Peter S. Spencer
Pentaborane	964	(2)
Steven A. Sparr
2,4-Pentanedione	966	(1)
Peter S. Spencer
Pentazocine	967	(1)
Herbert H. Schaumburg
Pentenenitrile	968	(1)
Mary Beth Genter
Kevin M. Crofton
Perhexilene Maleate	969	(2)
Steven Herskovitz
Pertussis Vaccine	971	(4)
Neil L. Rosenberg
Pfiesteria piscicida	975	(2)
Edward D. Levin
Howard Glasgow Jr.
Donald E. Schmechel
Nora Deamer-Melia
JoAnn Burkholder
Phalaris Spp.	977	(2)
Alexander Storch
Albert C. Ludolph
Phencyclidine	979	(6)
Daniel C. Javitt
Phenelzine and Other Monoamine Oxidase Inhibitors	985	(2)
Arnold E. Merriam
Phenol	987	(1)
Herbert H. Schaumburg
Phenytoin	988	(11)
Allison Mann
Mark J. Sinnett
Shlomo Shinnar
Philanthotoxin	999	(1)
Tom Piek
Physalia Toxin	1000	(3)
Michael K. Pugsley
Michael J. A. Walker
Phytolacca Spp.	1003	(1)
Albert C. Ludolph
Picrotoxin	1004	(1)
Albert C. Ludolph
eter S. Spencer
Piper methysticum	1005	(1)
Albert C. Ludolph
Piperazine	1006	(2)
Steven A. Sparr
α-Plecteurys tristis Toxins	1008	(1)
Albert C. Ludolph
Peter S. Spencer
Podophyllotoxin and Related Compounds	1008	(2)
Fung-Chow Chui
Polio Virus Vaccine	1010	(3)
Neil L. Rosenberg
Polychlorinated Biphenyls	1013	(2)
Herbert H. Schaumburg
Polymyxin	1015	(1)
Herbert H. Schaumburg
Poneratoxin	1016	(1)
Tom Piek
Praziquantel	1017	(2)
Steven A. Sparr
n-Propanol	1019	(1)
Peter S. Spencer
Propranolol and Other β-Adrenergic Receptor Antagonists	1019	(5)
Steven A. Sparr
Propylene Glycol	1024	(1)
Brent T. Burton
Pseudomonas Toxins	1025	(1)
Albert C. Ludolph
Psilocybin and Psilocin	1026	(1)
John C. M. Brust
Pteridium aquilinum	1027	(1)
Albert C. Ludolph
Peter S. Spencer
Pyrethroids	1028	(16)
Henk P. M. Vijverberg
Pyridoxine/Vitamin B6	1044	(4)
Herbert H. Schaumburg
Pyrimethamine	1048	(1)
Herbert H. Schaumburg
Pyriminil	1048	(2)
Albert C. Ludolph
Peter S. Spencer
Pyrithione	1050	(5)
Zarife Sahenk
Jerry R. Mendell
Quinacrine	1055	(1)
Byron A. Kakulas
Quinidine	1056	(1)
Herbert H. Schaumburg
Quinine	1057	(1)
Steven Herskovitz
3-Quinuclidinyl Benzilate	1058	(6)
Peter S. Spencer
Rabies Vaccine	1064	(3)
Neil L. Rosenberg
Reserpine	1067	(1)
John D. Rogers
Rhodactis howesii	1068	(1)
Albert C. Ludolph
Ricin	1068	(2)
Herbert H. Schaumburg
Peter S. Spencer
Rotenone	1070	(1)
Matthias Riepe
Rubella Vaccine	1071	(2)
Neil L. Rosenberg
Sarin, Other ``Nerve Agents'', and their Antidotes	1073	(20)
Peter S. Spencer
Barry W. Wilson
Edson X. Albuquerque
Saxitoxin	1093	(3)
Richard G. Pellegrino
Scombroid Fish (Histamine)	1096	(1)
Albert C. Ludolph
Peter S. Spencer
Scorpion Toxins (α and β)	1097	(2)
Albert C. Ludolph
Peter S. Spencer
Sea Anemone Toxins	1099	(1)
Albert C. Ludolph
Selenium	1100	(3)
Dennis J. Blodgett
Bernard S. Jortner
Shiga Toxin	1103	(1)
Albert C. Ludolph
Peter S. Spencer
Silicone	1104	(2)
Neil L. Rosenberg
Smallpox Vaccine	1106	(1)
Neil L. Rosenberg
Sodium Azide	1107	(3)
Mohammad I. Sabri
Spirogermanium	1110	(1)
Herbert H. Schaumburg
Stichodactyla Spp.	1111	(1)
Albert C. Ludolph
Peter S. Spencer
Stipa robusta	1112	(1)
Frank Bretschneider
Albert C. Ludolph
Stonefish Venom	1112	(2)
Albert C. Ludolph
Peter S. Spencer
Strychnine	1114	(2)
Charles N. Allen
Styrene	1116	(5)
John L. O'Donoghue
Succinylcholine	1121	(1)
Phyllis L. Bieri
Sulfasalazine	1122	(2)
Herbert H. Schaumburg
Sulfonamides	1124	(1)
Steven Herskovitz
Suramin Sodium	1125	(2)
Herbert H. Schaumburg
Swainsonine	1127	(4)
Steven U. Walkley
Tacrolimus	1131	(2)
Herbert H. Schaumburg
Albert C. Ludolph
Bruce G. Gold
Taicatoxin	1133	(1)
Albert C. Ludolph
Peter S. Spencer
Taipoxin	1134	(1)
Albert C. Ludolph
Taxoids	1135	(5)
Stuart C. Apfel
Tellurium	1140	(3)
Kenneth R. Reuhl
Marianne A. Polunas
Tetanospasmin	1143	(5)
John W. Griffin
George Oyler
Tetrachlorodibenzodioxin	1148	(3)
Marie Haring Sweeney
David A. Dankovic
1,1,2,2-Tetrachloroethane	1151	(3)
John L. O'Donoghue
Tetrachloroethylene	1154	(4)
John L. O'Donoghue
Tetracyclines	1158	(2)
Steven A. Sparr
Tetramethylthiuram Disulfide	1160	(2)
John L. O'Donoghue
Tetrodotoxin	1162	(1)
Toshio Narahashi
Thalicarpine	1163	(2)
Peter S. Spencer
Thalidomide	1165	(3)
Herbert H. Schaumburg
Thallium	1168	(9)
Luigi Manzo
Thiophene	1177	(2)
John L. O'Donoghue
Thymidine	1179	(1)
Herbert H. Schaumburg
Tick Saliva	1180	(2)
Rainer Gothe
Tityustoxin	1182	(1)
Albert C. Ludolph
Peter S. Spencer
Toluene	1183	(7)
Herbert H. Schaumburg
Toluene 2,4-Diisocyanate	1190	(1)
Herbert H. Schaumburg
Toxaphene and Constituents	1191	(2)
Peter S. Spencer
``Toxic Oil''	1193	(3)
Alberto Portera-Sanchez
Manuel Posada de la Paz
Tremetone	1196	(1)
Albert C. Ludolph
Triamcinolone	1197	(1)
Byron A. Kakulas
1,1,1-Trichloroethane	1198	(4)
John L. O'Donoghue
Trichloroethylene	1202	(1)
Herbert H. Schaumburg
Tricyclic Antidepressants	1203	(3)
Arnold E. Merriam
Triethyltin	1206	(3)
Georg J. Krinke
Trihexyphenidyl Hydrochloride	1209	(1)
John D. Rogers
Trimethaphan Camsylate	1209	(1)
Herbert H. Schaumburg
Trimethobenzamide Hydrochloride	1210	(1)
Herbert H. Schaumburg
Trimethyltin	1211	(3)
Georg J. Krinke
Triparanol	1214	(1)
Herbert H. Schaumburg
Trithiozine	1215	(1)
Steven Herskovitz
L-Tryptophan	1216	(3)
Herbert H. Schaumburg
Neil L. Rosenberg
d-Tubocurarine	1219	(3)
Phyllis L. Bieri
Valproic Acid	1222	(4)
Carol Eisenberg
Mark J. Sinnett
Shlomo Shinnar
Vecuronium Bromide	1226	(2)
Steven Herskovitz
Veratridine	1228	(1)
Albert C. Ludolph
Vidarabine	1229	(1)
Herbert H. Schaumburg
Vigabatrin	1230	(2)
Herbert H. Schaumburg
Vinca Alkaloids	1232	(4)
Herbert H. Schaumburg
Vinyl Chloride	1236	(3)
Peter S. Spencer
Vinyltoluene	1239	(1)
Herbert H. Schaumburg
Vitamin A	1239	(2)
Mitchell Steinschneider
Volkensin	1241	(2)
Albert C. Ludolph
Water	1243	(1)
Herbert H. Schaumburg
Yellow Star Thistle	1244	(2)
Dwijendra N. Roy
Peter S. Spencer
Zidovudine	1246	(7)
Enrica Arnaudo
Zimeldine	1253	(2)
Neil L. Rosenberg
Zolpidem	1255	(2)
Albert C. Ludolph
Appendix 1	1257	(12)
Appendix 2	1269	(8)
Index	1277